02437nas a2200265   4500008004100000245009200041210006900133300001100202490000700213520143600220653005301656653002601709653002201735653005701757653004501814653008601859100001601945700002001961700001501981700002101996700001802017700001502035700001502050856010602065       2007                        eng d00aPhylemon: a suite of web tools for molecular evolution, phylogenetics and phylogenomics0 aPhylemon a suite of web tools for molecular evolution phylogenet  aW38-420 v353 aPhylemon is an online platform for phylogenetic and evolutionary analyses of molecular sequence data. It has been developed as a web server that integrates a suite of different tools selected among the most popular stand-alone programs in phylogenetic and evolutionary analysis. It has been conceived as a natural response to the increasing demand of data analysis of many experimental scientists wishing to add a molecular evolution and phylogenetics insight into their research. Tools included in Phylemon cover a wide yet selected range of programs: from the most basic for multiple sequence alignment to elaborate statistical methods of phylogenetic reconstruction including methods for evolutionary rates analyses and molecular adaptation. Phylemon has several features that differentiates it from other resources: (i) It offers an integrated environment that enables the direct concatenation of evolutionary analyses, the storage of results and handles required data format conversions, (ii) Once an outfile is produced, Phylemon suggests the next possible analyses, thus guiding the user and facilitating the integration of multi-step analyses, and (iii) users can define and save complete pipelines for specific phylogenetic analysis to be automatically used on many genes in subsequent sessions or multiple genes in a single session (phylogenomics). The Phylemon web server is available at http://phylemon.bioinfo.cipf.es.10aAnimals Computational Biology/*methods Databases10aDNA Sequence Analysis10aGenetic Evolution10aMolecular Genetic Techniques Humans *Internet Models10aProtein Software User-Computer Interface10aStatistical *Phylogeny Programming Languages Sequence Alignment Sequence Analysis1 aTarraga, J.1 aMedina, Ignacio1 aArbiza, L.1 aHuerta-Cepas, J.1 aGabaldón, T.1 aDopazo, J.1 aDopazo, H.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1745234602859nas a2200301   4500008004100000245009400041210006900135300001300204490000800217520172300225653007401948653002202022653001902044653002402063653002802087653002002115653015502135653002502290100001502315700001402330700001702344700001602361700002202377700002202399700001502421700001502436856010602451       2006                        eng d00aSelective pressures at a codon-level predict deleterious mutations in human disease genes0 aSelective pressures at a codonlevel predict deleterious mutation  a1390-4040 v3583 aDeleterious mutations affecting biological function of proteins are constantly being rejected by purifying selection from the gene pool. The non-synonymous/synonymous substitution rate ratio (omega) is a measure of selective pressure on amino acid replacement mutations for protein-coding genes. Different methods have been developed in order to predict non-synonymous changes affecting gene function. However, none has considered the estimation of selective constraints acting on protein residues. Here, we have used codon-based maximum likelihood models in order to estimate the selective pressures on the individual amino acid residues of a well-known model protein: p53. We demonstrate that the number of residues under strong purifying selection in p53 is much higher than those that are strictly conserved during the evolution of the species. In agreement with theoretical expectations, residues that have been noted to be of structural relevance, or in direct association with DNA, were among those showing the highest signals of purifying selection. Conversely, those changing according to a neutral, or nearly neutral mode of evolution, were observed to be irrelevant for protein function. Finally, using more than 40 human disease genes, we demonstrate that residues evolving under strong selective pressures (omega<0.1) are significantly associated (p<0.01) with human disease. We hypothesize that non-synonymous change on amino acids showing omega<0.1 will most likely affect protein function. The application of this evolutionary prediction at a genomic scale will provide an a priori hypothesis of the phenotypic effect of non-synonymous coding single nucleotide polymorphisms (SNPs) in the human genome.10aAmino Acid Sequence Amino Acid Substitution Codon/*genetics Databases10aGenetic Evolution10aGenetic Models10aHuman Humans Models10aInborn/*genetics Genome10aMolecular Genes10aMolecular Molecular Sequence Data *Mutation Neoplasms/genetics Proteins/genetics *Selection (Genetics) Tumor Suppressor Protein p53/chemistry/genetics10ap53 Genetic Diseases1 aArbiza, L.1 aDuchi, S.1 aMontaner, D.1 aBurguet, J.1 aPantoja-Uceda, D.1 aPineda-Lucena, A.1 aDopazo, J.1 aDopazo, H.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16584746